Japanese Traditional Herbal Medicine, Rikkunshito, Partially Suppresses Inflammatory Responses in Myocardial Ischemia/Reperfusion Injury.

Abstract

Myocardial ischemia/reperfusion (I/R) injury can cause additional damage to an ischemic myocardium, even after successful reperfusion therapy. Inflammation is a mechanism that exacerbates myocardial damage after I/R injury. Rikkunshito(RKT) is a traditional Japanese herbal medicine widely used to treat gastrointestinal symptoms. It attenuates inflammation and fibrosis in some diseases of the heart; however, it remains unclear whether RKT exerts cardioprotective effects against myocardial I/R injury. To elucidate this, we evaluated the effects of RKT pre-treatment by oral administration on the myocardium in a mouse model of in vivo I/R injury. Mice were randomly assigned to a group receiving distilled water (DW) or one receiving RKT (1000 mg/kg/day) for 14 days orally. For each of the RKT and DW groups, a sham group, an I/R 2 h group, and an I/R 24 h group were created. On day 15, myocardial I/R surgery was performed. The left anterior descending coronary artery (LAD) was ligated for 30 min, and reperfusion time was set at 2 h or 24 h. The myocardial infarct size (IS) was measured after 2 h of reperfusion, and cardiac cytokine mRNA expression levels were evaluated by quantitative reverse transcription polymerase chain reaction (RT-PCR) after 2 h and 24 h of reperfusion. RKT pre-treatment significantly suppressed the cardiac mRNA expression level of interleukin-1β in the RKT-I/R 2 h group compared to the DW-I/R 2 h group (P < 0.05). Additionally, RKT significantly suppressed the mRNA expression levels of transforming growth factor-β compared to DW; the same result was obtained for the expression levels of interleukin-6. However, RKT did not reduce the IS or mRNA expression levels of the cardiac congestive markers natriuretic peptide a(NPPA) and natriuretic peptide b (NPPB). In addition, RKT did not alter the plasma concentration of ghrelin and sirtuin 1 (Sirt1), which have been reported to be stimulated by RKT. This study showed that pre-treatment of RKT for myocardial I/R injury partially suppressed inflammation-related cytokines. However, further studies are needed on the effect of RKT on the reduction of myocardial infarction size.